PWWP2B

Chr 10

PWWP domain containing 2B

Also known as: PWWP2, bA432J24.1, pp8607

PWWP2B encodes a chromatin-binding protein that acts as an adapter between nucleosome components and chromatin-modifying complexes, regulating histone acetylation levels at actively transcribed genes by forming NuRD subcomplexes and recruiting HDACs to gene promoters. Mutations cause neurodevelopmental disorders with intellectual disability and developmental delay. The gene follows autosomal dominant inheritance and is highly constrained against loss-of-function variants.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
97
P/LP submissions
0%
P/LP missense
0.49
LOEUF
LOF
Mechanism· predicted
Clinical SummaryPWWP2B
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.84) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
97 unique Pathogenic / Likely Pathogenic· 133 VUS of 251 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.841
Z-score 2.28
OE 0.00 (0.000.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.42Z-score
OE missense 0.81 (0.740.88)
338 obs / 419.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.49)
00.351.4
Missense OE0.81 (0.740.88)
00.61.4
Synonymous OE1.17
01.21.6
LoF obs/exp: 0 / 6.0Missense obs/exp: 338 / 419.6Syn Z: -1.92
DN
0.2997th %ile
GOF
0.2497th %ile
LOF
0.79top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.49

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

251 submitted variants in ClinVar

Classification Summary

Pathogenic92
Likely Pathogenic5
VUS133
Likely Benign10
92
Pathogenic
5
Likely Pathogenic
133
VUS
10
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
92
0
92
Likely Pathogenic
0
0
5
0
5
VUS
0
122
11
0
133
Likely Benign
0
9
1
0
10
Benign
0
0
0
0
0
Total01311090240

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PWWP2B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗